Oncological outcomes of fertility-sparing surgery versus radical surgery in stage - epithelial ovarian cancer: a systematic review and meta-analysis

Background The oncological outcomes of fertility-sparing surgery (FSS) compared to radical surgery (RS) in patients with stage I epithelial ovarian cancer (EOC) remain a subject of debate. We evaluated the risk ratios (RRs) for outcomes in patients with stage I EOC who underwent FSS versus RS. Methods We conducted a systematic search of PubMed, Web of Science, and Embase for articles published up to November 29, 2023. Studies that did not involve surgical procedures or included pregnant patients were excluded. We calculated the RRs for disease-free survival, overall survival, and recurrence rate. The quality of the included studies was assessed using the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. The meta-analysis was registered on PROSPERO (CRD42024546460). Results From the 5,529 potentially relevant articles, we identified 83 articles for initial screening and included 12 articles in the final meta-analysis, encompassing 2,906 patients with epithelial ovarian cancer. There were no significant differences between the two groups in disease-free survival (RR [95% confidence interval {CI}], 0.90 [0.51, 1.58]; P = 0.71), overall survival (RR [95% CI], 0.74 [0.53, 1.03]; P = 0.07), and recurrence rate (RR [95% CI], 1.10 [0.69, 1.76]; P = 0.68). In sensitivity analyses, the significant difference was observed only for overall survival (before exclusion: RR [95% CI], 0.74 [0.53–1.03], P = 0.07; after exclusion: RR [95% CI], 0.70 [0.50–0.99]; P = 0.04). Conclusions This is the first and only individual patient data meta-analysis comparing disease-free survival, overall survival, and recurrence rate of patients with early-stage epithelial ovarian cancer undergoing FSS and RS. FSS was associated with similar disease-free survival and risk of recurrence as RS. We hypothesized that the decreased overall survival in the FSS group could not be attributed to distant metastases from epithelial ovarian cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-024-03440-3.


Bias due to deviations from intended interventions
If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 4.1.Were there deviations from the intended intervention beyond what would be expected in usual practice?
Other clinicopathological factors, surgical procedures, and postoperative adjuvant therapy were similar between these groups.4.2.If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?
If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6 4.3.Were important co-interventions balanced across intervention groups?4.4.Was the intervention implemented successfully for most participants?4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?

Measured variable(s)
Is there evidence that controlling for this variable was unnecessary?

Additional co-interventions
Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?
Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator NA NA NA

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?
1. 3 If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?

Questions relating to baseline confounding only
1. 4 If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?
As presented in Table 2, patients who received chemotherapy were younger (P = 0.001), with higher grade (P= 0.017) and with larger tumor size (P < 0.001).
1.5 If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?
1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?
3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?

Risk of bias judgement
Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?
1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?

Risk of bias judgement
2.1 Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?
2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?
2. 3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?
2. 4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?
2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?
4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?

Bias in classification of interventions
3.1 Were intervention groups clearly defined?

Risk of bias judgement
Bias due to missing data 5.1 Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?
5. 4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?

Bias due to deviations from intended interventions
If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 4.1.Were there deviations from the intended intervention beyond what would be expected in usual practice?
There was no significant regarding the proportion of patients receiving chemotherapy (P = 0.479) or LN dissection (P = 0.396) between these two groups (Table 4).Among patients aged between 18 and 45 years old, we selected those with unilateral salpingo-oophorectomy and uterine preservation (FSS group) and those with bilateral salpingooophorectomy or hysterectomy (non-FSS) based on surgery codes of ovarian cancer to perform subgroup analysis.

Measured variable(s)
Is there evidence that controlling for this variable was unnecessary?

Bias in classification of interventions
3.1 Were intervention groups clearly defined?
Among patients aged between 18 and 45 years old, we selected those with unilateral salpingo-oophorectomy and uterine preservation (FSS group) and those with bilateral salpingooophorectomy or hysterectomy (non-FSS) based on surgery codes of ovarian cancer to perform subgroup analysis.
3.2 Was the information used to define intervention groups recorded at the start of the intervention?
3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?

Risk of bias judgement
Bias in selection of participants into the study

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?As presented in Table 2, patients who received chemotherapy were younger (P = 0.001), with higher grade (P= 0.017) and with larger tumor size (P < 0.001).

Bias in measurement of the outcome
6.1 Could the outcome measure have been influenced by knowledge of the intervention received?
6.2 Were outcome assessors aware of the intervention received by study participants?
6.3 Were the methods of outcome assessment comparable across intervention groups?
6.4 Were any systematic errors in measurement of the outcome related to intervention received?

Bias in selection of the reported result
Is the reported effect estimate likely to be selected, on the basis of the results, from…

Bias in selection of the reported result
Is the reported effect estimate likely to be selected, on the basis of the results, from… There was no significant regarding the proportion of patients receiving chemotherapy (P = 0.479) or LN dissection (P = 0.396) between these two groups (Table 4).

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?

Bias in classification of interventions
3.1 Were intervention groups clearly defined?
In most cases conservative surgery consisted of unilateral salpingo-oophorectomy with or without biopsy of controlateral ovary.
3.2 Was the information used to define intervention groups recorded at the start of the intervention?
3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?

Risk of bias judgement
Bias due to missing data

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?

Risk of bias judgement
Bias due to missing data 5.5 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?

Bias in selection of the reported result
Is the reported effect estimate likely to be selected, on the basis of the results, from… 7.1.... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?1.3 If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?

Questions relating to baseline confounding only
1. 4 If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?
1.5 If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?

Bias in selection of the reported result
Is the reported effect estimate likely to be selected, on the basis of the results, from…

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?
1.3 If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?

Questions relating to baseline confounding only
1. 4 If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?
There were no significant differences in the baseline data between the two groups except for age.

Bias in classification of interventions
3.1 Were intervention groups clearly defined?
FSS was defined as an operation that resulted in preservation of the uterus and the contralateral ovary.Patients who had undergone a prior hysterectomy and/or removal of the contralateral ovary were not included in the FSS group, and therefore included in the RS group.Forty-seven per cent (n = 50) of all evaluated patients received adjuvant chemotherapy.The rate of adjuvant treatment was 38% (n = 5) in the FSS group and 48% (n = 45) in the RS group (Table 1).

Risk of bias judgement
Bias in selection of the reported result  The median age of patients at diagnosis who underwent FSS was significantly younger (by 10 years), compared with those who underwent RS (p < 0.001).Patients in the RS group were more likely to have coexisting endometriosis (p = 0.006), which could be attributed to the higher proportion of clear-cell

Risk of bias judgement
Bias due to missing data Because the RS group included more high-grade and clear-cell tumors (p < 0.001) than the FSS group, the proportion of patients receiving adjuvant chemotherapy (p = 0.006) were higher in the RS group.

Bias in selection of the reported result
Is the reported effect estimate likely to be selected, on the basis of the results, from…

Additional co-interventions
Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

NA
NA NA

No
No information

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?
1.3 If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?

Questions relating to baseline confounding only
1. 4 If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?
The median age of patients at diagnosis who underwent FSS was significantly younger (by 10 years), compared with those who underwent RS (p < 0.001).Patients in the RS group were more likely to have coexisting endometriosis (p = 0.006), which could be attributed to the higher proportion of clear-cell

Co-interventions listed in the review protocol
Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

Additional co-interventions
Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

No
No information

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?The median age of patients at diagnosis who underwent FSS was significantly younger (by 10 years), compared with those who underwent RS (p < 0.001).Patients in the RS group were more likely to have coexisting endometriosis (p = 0.006), which could be attributed to the higher proportion of clear-cell

Bias due to deviations from intended interventions
If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 4.1.Were there deviations from the intended intervention beyond what would be expected in usual practice?
Because the RS group included more high-grade and clear-cell tumors (p < 0.001) than the FSS group, the proportion of patients receiving adjuvant chemotherapy (p = 0.006) were higher in the RS group.Lymphadenectomy P=0.317

Bias in selection of the reported result
Is the reported effect estimate likely to be selected, on the basis of the results, from…

Additional co-interventions
Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator
NA NA NA

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?Conservative surgical procedures are to preserve fertility (ie, unilateral salpingo-oophorectomy, wedge resection of the contralateral ovary, and omentectomy).Radical operations consist of simple total hysterectomy, bilateral salpingooophorectomy, and omentectomy, along with pelvic and 3.2 Was the information used to define intervention groups recorded at the start of the intervention?

Risk of bias judgement
Questions relating to baseline and time-varying confounding The treatment of chemotherapy was similar.

Additional co-interventions
Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

NA
NA NA

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?
1.3 If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?

Questions relating to baseline confounding only
1. 4 If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?
These women were significantly younger than the 47 patients who underwent RS (p < 0.001), and had a lower previous parity (p < 0.001).The women undergoing RS were more often diagnosed in stage IC-62% (29/47) vs. 25% (9/36) (p = 0.002).They also more often had tumors with highly aggressive They also more often had tumors with highly aggressive potential, were more often surgically staged with lymph node dissections, and were more likely to receive adjuvant chemotherapy (p = 0.003).FSS was defined as the preservation of the uterus and at least part of one ovary [16].RS was defined as hysterectomy with bilateral oophorectomy.FSS was defined as the preservation of the uterus and at least part of one ovary [16].RS was defined as hysterectomy with bilateral oophorectomy.
3.2 Was the information used to define intervention groups recorded at the start of the intervention?
3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?

Risk of bias judgement
Bias in selection of participants into the study

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?
1.3 If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?

Questions relating to baseline confounding only
1. 4 If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?
These women were significantly younger than the 47 patients who underwent RS (p < 0.001), and had a lower previous parity (p < 0.001).The women undergoing RS were more often diagnosed in stage IC-62% (29/47) vs. 25% (9/36) (p = 0.002).They also more often had tumors with highly aggressive They also more often had tumors with highly aggressive potential, were more often surgically staged with lymph node dissections, and were more likely to receive adjuvant chemotherapy (p = 0.003).

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?

Bias in classification of interventions
3.1 Were intervention groups clearly defined?
For the subgroup analysis, we selected patients who underwent unilateral salpingo-oophorectomy and uterine preservation for the FSS group and patients who underwent bilateral salpingooophorectomy or hysterectomy for the non-FSS group based on the surgical codes for ovarian cancer.
3.2 Was the information used to define intervention groups recorded at the start of the intervention?

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?

Bias in classification of interventions
3.1 Were intervention groups clearly defined?
FSS, defined as conservation of the uterus and at least part of one ovary, included unilateral cystectomy (UC) and unilateral salpingo-oophorectomy (USO).Radical surgery (RS) was defined as bilateral salpingo-oophorectomy or hysterectomy (with unilateral or bilateral salpingo-oophorectomy).All patients There was no significant difference between the FSS group and RS group regarding rate of chemotherapy.Appendectomy and lymphadenectomy were optional and carried out according to the surgeons' experience and intraoperative findings.

Bias due to confounding
1.1 Is there potential for confounding of the effect of intervention in this study?Patients who underwent fertility-sparing surgery were significantly younger than were those who underwent radical surgery (P =0.001)(Table 1).More patients in the radical surgery group had a history of abdominal surgery (P = 0.010) and a parity of at least one (P b 0.001), but no other significant Patients who underwent fertility-sparing surgery were significantly younger than were those who underwent radical surgery (P =0.001)(Table 1).More patients in the radical surgery group had a history of abdominal surgery (P = 0.010) and a parity of at least one (P b 0.001), but no other significant the confounding domain measured validly and reliably by this variable?OPTIONAL: Is failure to adjust for this variable (alone) expected to favour the experimental intervention or the comparator?

4. 2 . 6 4. 3 . 4 . 4 .
If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.Were important co-interventions balanced across intervention groups?Was the intervention implemented successfully for most participants?
the confounding domain measured validly and reliably by this variable?OPTIONAL: Is failure to adjust for this variable (alone) expected to favour the experimental intervention or the comparator?

7. 1 .
... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?as the time from diagnosis to death for any cause or to the last contact.
that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparatorChemotherapyNo No information Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator 1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?NA NA NA

PNA
total of 24 women underwent FSS for eEOC.Eighteen out of these were one-to-one matched and balanced for stage, histologic type, and grading with a group of patients who NA listed in the review protocol Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparatorConfounding domains listed in the review protocol that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator

PNA 1
total of 24 women underwent FSS for eEOC.Eighteen out of these were one-to-one matched and balanced for stage, histologic type, and grading with a group of patients who NA Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?

3. 1 2 . 1 1 2 4. 1 . 6 4. 3 . 4 . 4 .
Were intervention groups clearly defined?3.2 Was the information used to define intervention groups recorded at the start of the intervention?3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?5.5 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data? for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.Were there deviations from the intended intervention beyond what would be expected in usual practice?Adjuvant chemotherapy, P>0.99.4.2.If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.Were important co-interventions balanced across intervention groups?Was the intervention implemented successfully for most participants?4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?
Epidemiology, and End Results (SEER) database was utilized to identify patients diagnosed with stage I EEOC,OCCC, and MOC between January 2000 and December PN PN NA Confounding domains listed in the review protocol Additional confounding domains NA Co-interventions listed in the review protocol Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator Chemotherapy No No information Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator 1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?NA NA NA

3. 2 2 4. 1 .
Was the information used to define intervention groups recorded at the start of the intervention?3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?Risk of bias judgementRisk of bias judgementBias due to missing data5.1 Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4  If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions? for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.Were there deviations from the intended intervention beyond what would be expected in usual practice?

Y
clinical and pathological or follow-up information and those with disease extending beyond stage I and undergoing FSS were also excluded.Patients were contacted by telephone or letter to obtain regular follow-up information when it was not available.PN PN NA Additional confounding domains NA Co-interventions listed in the review protocol Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator Confounding domains listed in the review protocol Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?Additional co-interventions Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator NA NA NA No No information

5. 1 your aim for this study is to assess the effect of assignment to intervention, answer questions 4 .1 and 4. 2 4. 1 .
Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4  If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?Were there deviations from the intended intervention beyond what would be expected in usual practice?

4. 2 . 6 4. 3 . 4 . 4 .
If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.Were important co-interventions balanced across intervention groups?Was the intervention implemented successfully for most participants?4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?clinical and pathological or follow-up information and those with disease extending beyond stage I and undergoing FSS were also excluded.PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?

7. 1 . 1
... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?Risk of bias judgementAdditional confounding domainsNACo-interventions listed in the review protocolIs there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

1. 5
If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?clinical and pathological or follow-up information and those with disease extending beyond stage I and undergoing FSS were also excluded.by telephone or letter to obtain regular follow-up information when it was not available.using histologic evidence of disease via tumor biopsy, fine-needle biopsy, or the appearance of new lesions on imaging examination.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?

3. 1 1 1
Were intervention groups clearly defined?Fertility-sparing surgery included ipsilateral adnexectomy and biopsy or wedge excision of contralateral ovary.Radical surgery included hysterectomy and bilateral adnexectomy.Two independent pathologists with extensive experience in gynecological pathology reviewed all of the pathological slides 3.2 Was the information used to define intervention groups recorded at the start of the intervention?3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?Risk of bias judgement Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?5.5 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?

4. 2 .
If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6 4.3.Were important co-interventions balanced across intervention groups?4.4.Was the intervention implemented successfully for most participants?4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?

7. 1 . 1
... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?

Y
No patients were lost to follow-up.PNPNNAIs presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparatorConfounding domains listed in the review protocolAdditional confounding domainsNACo-interventions listed in the review protocolIs there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

4. 2 . 6 4. 3 . 4 . 4 . 1 Y
If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.Were important co-interventions balanced across intervention groups?Was the intervention implemented successfully for most participants?PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?During the study period 83 women aged 18-40 years diagnosed with EOC and with complete data, were identified in the SQRGC.There were 11 patients who were excluded due to PN PN NAIs presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparatorConfounding domains listed in the review protocolAdditional confounding domainsNACo-interventions listed in the review protocolIs there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?

1. 5 3 . 3 Risk of bias judgement 2 . 1 1 your aim for this study is to assess the effect of assignment to intervention, answer questions 4 .1 and 4. 2 4. 1 .
If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?Risk of bias judgement Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?Were there deviations from the intended intervention beyond what would be expected in usual practice?

4. 2 . 6 4. 3 . 4 . 4 .
If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.Were important co-interventions balanced across intervention groups?Was the intervention implemented successfully for most participants?

3. 2 3 . 1
Was the information used to define intervention groups recorded at the start of the intervention?Were intervention groups clearly defined?

1. 5 1 1 1 2 4. 1 .
If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?Additional co-interventionsIs there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparatorIs there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?Is the reported effect estimate likely to be selected, on the basis of the results, from… 7.1.... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?period 83 women aged 18-40 years diagnosed with EOC and with complete data, were identified in the SQRGC.There were 11 patients who were excluded due to PN PN NA NA Low N Survival estimates included overall survival (OS), calculated from the date of diagnosis to either the date of death from any cause or the date of data retrieval.Is the reported effect estimate likely to be selected, on the basis of the results, from… 7.1.... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?5.5 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data? for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.Were there deviations from the intended intervention beyond what would be expected in usual practice?

4. 2 .
If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6 4.3.Were important co-interventions balanced across intervention groups?4.4.Was the intervention implemented successfully for most participants?4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?
if they met any of the following criteria: lack of histologic confirmation, stage II-IV or unknown stage, receipt of radiation therapy, recommended surgery not NA Epidemiology, and End Results (SEER) database was utilized to identify patients diagnosed with stage I EEOC,OCCC, and MOC between January 2000 and December PN PN NA Confounding domains listed in the review protocol Additional confounding domains NA Co-interventions listed in the review protocol Is there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator Chemotherapy No No information Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator 1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?NA NA NA

N
There was no significant difference between the FSS group and RS group regarding preoperative CA125 value, frequency of complete staging surgery, distribution of FIGO stage, rate of NA study was carried out using data from the computerized database at Peking Union Medical College Hospital (PUMCH).One hundred and fifty-nine consecutive NA were obtained from inpatient and outpatient records, including demographics, clinical features, surgical procedures, pathological findings, adjuvant chemotherapy, PN PN NAAdditional confounding domainsNACo-interventions listed in the review protocolIs there evidence that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparatorConfounding domains listed in the review protocol that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator

3. 2 2 . 1 your aim for this study is to assess the effect of assignment to intervention, answer questions 4 .1 and 4. 2 4. 1 .
Was the information used to define intervention groups recorded at the start of the intervention?3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?Risk of bias judgement Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Risk of bias judgement Bias due to missing data 5.1 Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?Were there deviations from the intended intervention beyond what would be expected in usual practice?
Database was accessed, and a cohort of patients diagnosed between January 2004 and December 2015 with a pathologically confirmed primary ovarian carcinoma PN PN NA Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator that controlling for this co-intervention was unnecessary (e.g. because it was not administered)?Is presence of this co-intervention likely to favour outcomes in the experimental intervention or the comparator NA NA NA

1. 2 Questions relating to baseline confounding only 1 . 4
If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?1.3If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?

3 . 1 2 . 1 1 . 1 Questions relating to baseline confounding only 1 . 4
Were intervention groups clearly defined?3.2 Was the information used to define intervention groups recorded at the start of the intervention?3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Is there potential for confounding of the effect of intervention in this study?1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?1.3 If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?If N/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?

Risk of bias judgement Bias due to deviations from intended interventions If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 4
If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?.1.Were there deviations from the intended intervention beyond what would be expected in usual practice?
7.1.... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?

If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6
4.2.If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?

of bias judgement Bias in selection of participants into the study
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?1.3If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?Questions relating to baseline confounding only1.4IfN/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?1.5 If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?Risk 2.1 Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Risk of bias judgement 4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?

Bias due to deviations from intended interventions If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2
5.1 Were outcome data available for all, or nearly all, participants?

Is there evidence that controlling for this variable was unnecessary? Yes Measured variable(s) Is there evidence that controlling for this variable was unnecessary? Is the confounding domain measured validly and reliably by this variable? OPTIONAL: Is failure to adjust for this variable (alone) expected to favour the experimental intervention or the comparator?
7.1.... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?Risk of bias judgement 6.1 Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?Risk of bias judgement Unique ID Measured variable(s)

of bias judgement Bias in selection of participants into the study
1.5 If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?Risk 2.1 Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Risk of bias judgement 4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?

your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6
If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?

Risk of bias judgement Questions relating to baseline and time-varying confounding
Was the information used to define intervention groups recorded at the start of the intervention?3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?
1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?Risk

of bias judgement Bias in selection of participants into the study
2.1 Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Bias due to confounding1.1Istherepotentialforconfounding of the effect of intervention in this study?1.2IfY/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?1.3If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?Questions relating to baseline confounding only1.4IfN/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?

Is there evidence that controlling for this variable was unnecessary? Is the confounding domain measured validly and reliably by this variable?
1.5 If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?
3.1 Were intervention groups clearly defined?Fertility-sparing surgery included ipsilateral adnexectomy and biopsy or wedge excision of contralateral ovary.Radical surgery included hysterectomy and bilateral adnexectomy.Two independent pathologists with extensive experience in gynecological pathology reviewed all of the pathological slides 3.2 Was the information used to define intervention groups recorded at the start of the intervention?3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?Measured variable(s)

If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 4
.1.Were there deviations from the intended intervention beyond what would be expected in usual practice?Because the RS group included more high-grade and clear-cell tumors (p < 0.001) than the FSS group, the proportion of patients receiving adjuvant chemotherapy (p = 0.006) were higher in the RS group.Lymphadenectomy P=0.317 4.2.If Y/PY to 4.1: Were these deviations from intended intervention unbalanced between groups and likely to have affected the outcome?

If your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6
Is the reported effect estimate likely to be selected, on the basis of the results, from… 7.1.... multiple outcome measurements within the outcome domain?7.2 ... multiple analyses of the intervention-outcome relationship?7.3 ... different subgroups?

s) Is there evidence that controlling for this variable was unnecessary? Yes Measured variable(s) Is there evidence that controlling for this variable was unnecessary? Is the confounding domain measured validly and reliably by this variable? OPTIONAL: Is failure to adjust for this variable (alone) expected to favour the experimental intervention or the comparator?
Measured variable(

Bias in selection of participants into the study Risk of bias judgement Bias due to missing data
1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?1.8.If Y/PY to 1.7: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?Risk of bias judgement2.1 Was selection of participants into the study (or into the analysis) based on participant characteristics observed after the start of intervention?2.2 If Y/PY to 2.1: Were the post-intervention variables that influenced selection likely to be associated with intervention?2.3 If Y/PY to 2.2: Were the post-intervention variables that influenced selection likely to be influenced by the outcome or a cause of the outcome?2.4 If N/PN to 2.1: Do start of follow-up and start of intervention coincide for most participants?2.5.If Y/PY to 2.2 and 2.3, or N/PN to 2.4: Were adjustment techniques used that are likely to correct for the presence of selection biases?4.5.Did study participants adhere to the assigned intervention regimen?4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?5.1 Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4 If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?Bias

due to deviations from intended interventions If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 4
.1.Were there deviations from the intended intervention beyond what would be expected in usual practice?

of bias judgement Bias in selection of participants into the study
1.2 If Y/PY to 1.1: Was the analysis based on splitting participants' follow up time according to intervention received?1.3If Y/PY to 1.2: Were intervention discontinuations or switches likely to be related to factors that are prognostic for the outcome?Questions relating to baseline confounding only1.4IfN/PN to 1.2 or 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains?Further subgroup analysis according to tumor stage and histological grade did not show a worse OS with FSS in stage I EEOC patients.Further subgroup analysis did not show a worse OS with FSS in stage I MOC patients with any substage or histological grade.In the univariate analysis of the cohort of 1.5 If Y/PY to 1.4: Were confounding domains that were controlled for measured validly and reliably by the variables available in this study?1.6.If N/PN to 1.2 or 1.3: Did the authors control for any post-intervention variables that could have been affected by the intervention?Questions relating to baseline and time-varying confounding 1.7.If Y/PY to 1.3: Did the authors use an appropriate analysis method that controlled for all the important confounding domains and for time-varying confounding?Risk 4.6.If N/PN to 4.3, 4.4 or 4.5: Was an appropriate analysis used to estimate the effect of starting and adhering to the intervention?

Risk of bias judgement Risk of bias judgement Bias due to missing data
3.3 Could classification of intervention status have been affected by knowledge of the outcome or risk of the outcome?
5.1 Were outcome data available for all, or nearly all, participants?5.2 Were participants excluded due to missing data on intervention status? 5.3 Were participants excluded due to missing data on other variables needed for the analysis?5.4If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Are the proportion of participants and reasons for missing data similar across interventions?

If your aim for this study is to assess the effect of assignment to intervention, answer questions 4.1 and 4.2 4
.1.Were there deviations from the intended intervention beyond what would be expected in usual practice?

your aim for this study is to assess the effect of starting and adhering to intervention, answer questions 4.3 to 4.6
If PN/N to 5.1, or Y/PY to 5.2 or 5.3: Is there evidence that results were robust to the presence of missing data?Could the outcome measure have been influenced by knowledge of the intervention received?6.2 Were outcome assessors aware of the intervention received by study participants?6.3 Were the methods of outcome assessment comparable across intervention groups?6.4 Were any systematic errors in measurement of the outcome related to intervention received?